Project Summary/Abstract The overall goal of the proposed research is to advance policy approaches to support Precision Medicine research (PMR) with American Indian and Alaska Native (AIAN) people through culturally respectful dialogue, empiric data collection, and deliberation with rural and urban AIAN community members and tribal representatives in Alaska and Montana. We propose to address three complex and important challenges to conducting PMR within a successful community-academic partnership involving AIAN communities: (1) alignment of PMR with tribal health priorities; (2) return of PMR results to participants and communities; and (3) data stewardship. Understanding the importance of PM relative to other tribal health priorities, and how PM may benefit AIAN people, is an important first step in developing a clear understanding of the kinds of PMR that could be pursued and its potential value to AIAN communities. Identifying cultural, logistical, and environmental factors that must be considered is an essential first step because these factors influence the acceptability of PMR within AIAN communities, community members? willingness to participate, and ultimately, the uptake and usefulness of results and interventions that emerge from PMR. Flexible, community-responsive approaches to the return of results from PMR need to be developed. AIAN community members want to be involved in defining best practices for returning research results that maximize benefit and minimize risk for AIAN people. Moreover, developing trustworthy approaches to data stewardship ? who owns research information, whether it can be shared and with whom, and who decides ? is required if PMR is to move forward in AIAN communities. The proposed research will identify principles and approaches that can provide the foundation for effective PMR in AIAN communities. In collaboration with our AIAN Community Advisory Groups, we will: (1) Conduct empiric data collection from stakeholders at each study site, to understand community views regarding PM and PMR participation; (2) Convene local dialogs with tribal leadership at each site to review Aim 1 findings and discuss tribal health priorities, return of research results, and data stewardship, in addition to holding cross-site deliberation among AIAN tribal leaders in Alaska and Montana to identify areas of common ground and disagreement on these issues; (3) Develop a comprehensive communication plan to chart key messages, audiences, and communication vehicles for each study site to share the results emerging from this work with a full range of stakeholders, including other tribal organizations, researchers working with tribal communities, and research funders; and (4) Convene a national meeting to identify areas of consensus and challenges to be overcome in implementing PMR in AIAN communities.